As early as the 1870s, it was observed that mental activity influences regional brain physiology. Several researchers demonstrated that the surface pulsations and the temperature of the brain increase with mental activity. The technology necessary to pursue this research was limited, and it was not until the 1950s that the first instrument for quantifying whole brain blood flow and metabolism in humans was developed. Though the mechanisms coupling neuronal activation and vascular response are not fully understood, it is generally accepted that neural activation triggers vasodilation of the supplying vessels, thereby increasing blood flow to activated areas in the brain.
Various modalities have been developed for functional brain imaging. Techniques such as electroencephalography (EEG) and magenetoencephalography (MEG) measure the electromagnetic fields produced during neuronal activation to map brain function. Other techniques such as functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional transcranial Doppler sonography (fTCD) measure changes in blood flow or blood gas concentration as surrogates for detecting changes in neuronal activation.
The introduction of transcranial Doppler sonography (TCD) provided a non-invasive means to monitor blood flow through the major cerebral vessels in real-time using ultrasound. Functional TCD (fTCD) is the application of TCD for monitoring task-specific changes in cerebral blood flow. Early studies in fTCD focused on arterial velocity changes evoked through a simple light stimulation of the eye. Significant velocity changes were observed, particularly in the posterior cerebral artery (PCA), the principal vessel supplying the primary visual cortex. The range of studies has since expanded to include colored light, field-of-vision, half-field stimulation, intermittent stimulation, and stimulation with complex images. Changes in blood flow through the middle cerebral artery (MCA) associated with a specific stimulation have also been demonstrated. These studies focused on auditory stimulation, cognitive tasks, language, memory tests, and motor tasks. These studies were validated through direct comparison against the Wada test, which uses an anesthetic for lateral suspension of brain activity, and against fMRI, and established fTCD as a viable complementary tool for functional brain imaging. Functional TCD has since been applied to the study of migraines, stroke recovery, Alzheimer's disease, Parkinson's disease, Huntington's disease, and schizophrenia.
Compared to other brain imaging systems such as PET, SPECT, and MRI, TCD is a rapid, portable, inexpensive, continuous monitoring technique that can be applied to subjects and in settings unsuitable for study by other neuroimaging techniques. Functional TCD is limited, however, in its ability to localize regions of activity; TCD can only be used to measure flow through larger segments of the cerebral vasculature that supply blood to large regions of the brain spanning multiple functional areas because the signal backscattered by blood is significantly less than that backscattered by tissue. In addition, the skull significantly attenuates ultrasound; researchers have reported the attenuation of the skull to be 13 dB/cm/MHz. Therefore, to measure blood flow, TCD is generally limited to application through the three “acoustic windows,” including the temporal bone window, the orbital window, and the foramen magnum window. Use of only these three windows for this purpose limits the regional access available with fTCD. Furthermore, 5-8% of the population do not have any adequate acoustic window for applying TCD.
Thus, it would be desirable to provide more robust and less limited techniques for imaging brain functions.